Increasing use of ICU resources by an aging population has given rise to a new medical syndrome - "chronic critical illness" - characterized by derangements of multiple organs, recurrent nosocomial infections, and protracted dependence on mechanical ventilation and other life-sustaining therapies. Already numbering more than 100,000, the chronically critically ill are a growing population of older adults and a serious national health problem. Annual expenditures for these patients are estimated at $24 billion, mostly attributed to patients = 65 years old. Yet prognosis for patients with chronic critical illness is very poor: the majority die within 6 months, and survivors are severely functionally dependent. Half of these patients remain mechanically ventilated, even after prolonged, aggressive treatment. In addition, symptom distress is prevalent at high levels of intensity. This R21 application proposes a novel exploratory study focusing on relief of dyspnea during attempts to wean chronically critically ill older adults from mechanical ventilation. Dyspnea during weaning is common, reported by 40% of patients with chronic critical illness, and is an attractive target for intervention because treatment may not only alleviate suffering but also facilitate liberation of patients from mechanical ventilation. We hypothesize that pre-treatment with morphine will relieve dyspnea during weaning, improve cardiopulmonary physiologic parameters, and reduce patients' requirements for ventilatory support, without treatment-limiting side effects. Our Specific Aims are 1) To identify the most appropriate scale for assessing dyspnea in mechanically-ventilated older adults with chronic critical illness; 2) To evaluate, using the most appropriate scale, the effect of pre-treatment with intravenous morphine on dyspnea during weaning of chronically critically ill older adults from mechanical ventilation; 3) To estimate the effect size of this "pre-emptive" dyspnea treatment on physiologic parameters (including patient respiratory rate and tidal volume), duration of weaning trials, overall weaning success, and time to ventilator independence; 4) To examine the incidence of potential morphine-related side effects (nausea, sedation, delirium, constipation, respiratory depression) of the dyspnea treatment under study. We will conduct a randomized, double-blinded, placebo-controlled, pilot trial of morphine vs. normal saline, to be administered intravenously before weaning trials. Main outcomes will be patients' dyspnea ratings, pulmonary physiologic parameters, and tolerance of weaning. The setting will be our hospital's Respiratory Care Unit, a nationally-recognized center for treatment of chronically critically ill older adults who have undergone tracheotomy after failing multiple ICU weaning attempts. Our exploratory interventional study will provide essential preliminary data and methodologic guidance for a future, larger-scale, trial, in which we will test more definitively whether our intervention improves other important outcomes of chronic critical illness (including overall success in and time to ventilator independence), along with symptom control. Not applicable. [unreadable] [unreadable] [unreadable]